HELIOS: a microcosm of Asian health with global reach

When John Chambers first shared his genetic studies on Asian populations in London two decades ago, they were scientifically accepted but the international response was muted. “They weren’t always taken seriously,” Chambers, a cardiovascular epidemiologist recalls, “partly because they focused on a small migrant group in London. And that’s not where most Asians live.”

One of those early studies, published in 2014¹, analysed the full genetic sequence of more than 300 South Asians and revealed millions of previously undocumented genetic variants. It helped show why South Asians are more vulnerable to conditions such as diabetes and heart disease. However, it had become clear to Chambers, who was based at Imperial College London at the time, that the research needed to be rooted in Asia, to fully capture the region’s cultural, behavioural and genetic diversity.

In 2015 he got a call from James Best, then the dean of the Lee Kong Chian School of Medicine at Nanyang Technological University (NTU) in Singapore, which was at the beginning of a collaboration with Imperial and Singapore’s National Healthcare Group to create a state-of-the-art cohort study. Best wanted Chambers involved as one of the six principal investigators.

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It marked the start of an ambitious longitudinal population cohort study called Health for Life in Singapore (HELIOS). Since it began in 2018, HELIOS has recruited 10,004 people across Singapore’s three main ethnic groups — Chinese, Malay and Indian — and is collecting an unusually rich set of biological, clinical, behavioural and environmental data. The goal is to understand why Asian populations face such high rates of chronic disease, and how prevention, diagnosis and treatment can be improved.

“Cardiovascular mortality has dropped dramatically in the US and Europe over the past two decades,” says Chambers, who is now based at NTU. “But in Asia it’s gone the other way.”

There are around 296 million people in Asia with diabetes, more than half the estimated 589 million adults around the world with the condition. Cardiovascular disease deaths in Asia rose by 93% from 5.6 million in 1990 to 10.8 million in 2019, whereas the population only increased by 45%. Despite these trends, people of Asian ancestry remain under-represented in global biomedical studies.

As Singapore’s population grows older and chronic disease rates rise, the need for well-designed, long-term health studies has grown. By 2030, one in four Singaporean citizens will be aged 65 or older, and already around one in three adults has high blood pressure or high cholesterol.

Anurag Agrawal, dean of biosciences and health research at Ashoka University in Sonipat, India, says that large, long-term health studies that collect detailed biological and lifestyle data, such as HELIOS, are key to closing this gap. “They are some of the richest sources of information from which biological insights can be gleaned and it is critical that people of the south and southeast Asian regions be represented,” he says. It is particularly important as artificial intelligence becomes “the language of biology”, he adds, with growing use of machine learning to analyse biological data, detect patterns and guide health-care decisions.

The HELIOS participants, aged 30 to 84, undergo extensive baseline phenotyping, including bone-density scans, retinal imaging, electrocardiograms and testing for lung function and physical fitness. They provide blood, urine, saliva, stool and skin cell samples. They also complete detailed lifestyle, dietary and mental-health questionnaires, all validated in local languages. This is all taken over three to four hours, as participants move through 11 dedicated stations, each focused on a different aspect of health.

It sounds onerous but HELIOS has budding participants lining the block, keen to receive a comprehensive analysis of their health that dedicated doctors will assess. Participants will be contacted if previously unknown health issues surface in the results. “At one point the waiting list was 12 months,” Chambers laughs. “It’s been an amazing success.”

Data from the study are already revealing health disparities among ethnic groups². Indian and Malay participants show higher rates of diabetes, high blood pressure, obesity and anxiety symptoms than Chinese participants, despite reporting higher physical activity and, in some cases, better diet quality. “A huge global conundrum is why South Asians have a higher risk of diabetes than Europeans,” Chambers says. “What’s often not appreciated is those same disparities exist even within Asian populations.”

The detail of the HELIOS study means that researchers can build an in-depth picture of participants. It combines whole-genome sequencing to identify genetic variation, RNA sequencing to capture gene activity, and metabolomic profiling to measure compounds in the blood related to diet and disease. These data are linked to national health records — including laboratory tests, prescriptions and clinical diagnoses — providing researchers with a long-term view of each participant’s health across multiple systems.

“This is a step change in how we assess diet and health,” Chambers says. Most studies rely on asking participants to recall how often, or what, they ate “but let’s be honest, most people can’t remember what they ate yesterday”. Instead, HELIOS uses what’s known as plasma phenotyping: analysing chemical markers in the blood to identify diet-related biological patterns without relying on self-reporting. It “lets us identify dietary phenotypes objectively, at scale, across hundreds of thousands of samples”, Chambers says.

A recent analysis³ used data from HELIOS to identify a genetic variant that alters the levels of a coenzyme involved in removing cholesterol from the blood stream, reducing the efficiency of cholesterol transport, and which is common in Asians but rare or absent in other populations, he says. “That’s why its effect is so much more visible in our cohort.” It’s exactly the kind of region-specific insight HELIOS was built to reveal, and a reminder of why diverse representation in biomedical research matters.

Jimmy Lee Chee Keong, one of the six principal investigators on HELIOS, and a psychiatrist in the National Healthcare Group, says that at the project’s conception both academic and health-care leaders were thinking about “how to drive the health insights of the future”.